A First-in-human Study to Evaluate the Safety and Tolerability of AZD8853 in Participants with Selected Advanced/Metastatic Solid Tumours

Study identifier:D9450C00001

ClinicalTrials.gov identifier:NCT05397171

EudraCT identifier:2021-005438-41

CTIS identifier:N/A

Terminated/Withdrawn

Official Title

A Phase I/IIa First-in-human, Open-label Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of AZD8853 in Participants with Selected Advanced/Metastatic Solid Tumours

Medical condition

Urinary Bladder Neoplasms

Phase

Phase 1/2

Healthy volunteers

Study drug

AZD8853, Zirconium-89 crefmirlimab berdoxam

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 07 Jun 2022

Primary Completion Date: 06 Jun 2023

Study Completion Date: 06 Jun 2023

Study design

Allocation: Non-randomized
Endpoint Classification: -
Intervention Model: Sequential Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Sept 2024 by AstraZeneca

Collaborators

ImaginAb, Inc.

Inclusion and exclusion criteria

Inclusion Criteria

*
All Substudies:
1. At least one measurable target lesions per RECIST 1.1.
2. Eastern Cooperative Group (ECOG) of 0-1.
3. Life expectancy of ≥ 12 weeks
4. Adequate organ and marrow function as defined in the protocol
Substudy 1:
1. Histologically or cytologically confirmed locally advanced, unresectable or metastatic
NSCLC, MSS-CRC, or UC.
2. Documented progression from previous therapy
3. NSCLC:
3.a. At least 1 line of systemic therapy in the advanced / metastatic setting
3.b.Must have received anti-PD-1/anti-PD-L1 agent with or without chemotherapy
3.c. Part B and C: Documented no sensitizing EGFR mutations or ALK fusions/rearrangements
4. MSS-CRC:
4.a. At least 2 prior lines of systemic therapy in the advanced / metastatic setting, including specific therapies defined in the protocol
5. UC:
5.a. At least 1 prior line of systemic therapy in the advanced / metastatic setting, including either a platinum-containing regimen and/or an anti-PD-1 or anti-PD-L1 drug
6. Provision of archival tissue or unstained slides
7. Part B: Willing to provide mandatory biposies at screening and on study
8. Part B-CD8+ PET: At least 1 non-liver lesion suitable for PET imaging
*Key

Exclusion Criteria

*
All Substudies:
1. Unresolved toxicities ≥ Grade 2 per CTCAE 5.0 from prior therapy, with some exceptions defined in the protocol
2. Symptomatic CNS metastases or leptomeningeal disease
3. Active or ongoing infections, or uncontrolled intercurrent illness as defined in the protocol
4. Active or prior documented autoimmune or inflammatory disorder
5. Body weight loss of > 10% within 30 days of screening visit
6. Type 2 diabetes requiring management by metformin, where metformin cannot be switched to another treatment at least 7 days prior to starting study treatment
Substudy 1:
1. Must not have had a toxicity from a checkpoint inhibitor that lead to permanent discontinuation of immunotherapy
2. Participants with brain metastases, unless treated, asymptomatic, stable, and not requiring treatment

Location

Research Site

Providence, RI, United States, 02903

Location

Research Site

Saint Louis, MO, United States, 63110

Location

Research Site

Atlanta, GA, United States, 30322

Location

Research Site

Ottawa, ON, Canada, K1H 8L6

Location

Research Site

Toronto, Ontario, Canada, M5G 1X5

Location

Research Site

Seattle, WA, United States, 98109

Arms	Assigned Interventions
Experimental: Substudy 1 - Parts A, B, and C -Part A: AZD8853 monotherapy dose escalation -Part B1 and Part B2: AZD8853 monotherapy safety expansion at dose levels and indications determined to be safe in Part A -Part C1 and Part C2: AZD8853 monotherapy safety and preliminary efficacy expansion at dose levels and indications determined to be safe in Parts A and B	Drug: AZD8853 Monotherapy given until progressive disease or upon meeting other discontinuation criteria.
Experimental: Substudy 1 - Parts B1 and B2 with CD8+ PET Sub-set of participants from Parts B1 and B2 will also receive investigational CD8+ T cell targeted radioactive tracer, Zirconium-89 crefmirlimab berdoxam with PET scans	Drug: Zirconium-89 crefmirlimab berdoxam CD8+ T cell tracer for positron emission tomography (PET) at two time points in addition to monotherapy AZD8853 Other Name: 89-Zr-Df-IAB22M2C, 89-Zr-Df-crefmirlimab

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study was conducted from 07 Jun 2022 to 06 Jun 2023 at multiple centers in the United States of America and Canada.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants who met the inclusion criteria and none of the exclusion criteria were enrolled to the study. All study assessments were performed as per the schedule of assessment. Due to early termination of the study, only Part A was started, Parts B & C were not started.

Reporting Groups

	Description
AZD8853 300 mg	Participants with advanced/metastatic solid tumors received AZD8853 300 milligrams (mg) every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 1000 mg	Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 3000 mg	Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.

Participant Flow: Overall Study

	AZD8853 300 mg	AZD8853 1000 mg	AZD8853 3000 mg
STARTED	3	6	7
COMPLETED	0	0	0
NOT COMPLETED	3	6	7
Death	2	3	3
Study Terminated By Sponsor	1	2	3
Withdrawal by Subject	0	1	1

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Safety set included all participants who received any amount of investigational product (IP).

Reporting Groups

	Description
AZD8853 300 mg	Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 1000 mg	Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 3000 mg	Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.

Baseline Measures

	AZD8853 300 mg	AZD8853 1000 mg	AZD8853 3000 mg	Total
Number of Participants [units: Participants]	3	6	7	16
Age Continuous [units: Years] Mean ± Standard Deviation	62.0 ± 13.2	62.8 ± 4.2	65.1 ± 7.4	63.7 ± 7.3
Race/Ethnicity, Customized [units: Participants]
White	3	5	5	13
Not reported	0	1	1	2
Other	0	0	1	1
Sex: Female, Male [units: Participants]
Female	NA ^[1]	2	3	NaN
Male	NA ^[1]	4	4	NaN

Outcome Measures

1. Primary Outcome Measure: Number of Participants with Treatment-emergent Adverse Events (TEAEs) [ Time Frame: From Day 1 up to 90 (±7 days) days after the last dose of AZD8853 (1 Year) ]

Measure Type	Primary
Measure Name	Number of Participants with Treatment-emergent Adverse Events (TEAEs)
Measure Description	The safety and tolerability of AZD8853 in participants with selected advanced/metastatic solid tumors was assessed. As per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0, severity scale ranged from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event. This outcome measure was assessed only for substudy 1 Part A.
Time Frame	From Day 1 up to 90 (±7 days) days after the last dose of AZD8853 (1 Year)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety set included all participants who received any amount of IP.

Reporting Groups

	Description
AZD8853 300 mg	Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 1000 mg	Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 3000 mg	Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.

Measured Values

	AZD8853 300 mg	AZD8853 1000 mg	AZD8853 3000 mg
Number of Participants Analyzed [units:participants]	3	6	7
Number of Participants with Treatment-emergent Adverse Events (TEAEs) [units: Participants]
Any AE	3	4	6
Any AE possibly related to treatment	1	0	2
Any serious adverse event (SAE)	1	3	2
Any SAE possibly related to treatment	0	0	0
Any SAE with outcome death	0	1	0
Any SAE with outcome death and possibly related to treatment	0	0	0
Any AE leading to discontinuation of IP	0	1	0
Any AE leading to discontinuation of IP and possibly related to treatment	0	0	0
Any AE leading to interruption of IP	0	1	1
Any SAE leading to discontinuation of IP	0	1	0
Any SAE leading to discontinuation of IP and possibly related to treatment (IP)	0	0	0
Any AE of greater than or equal to (>=) CTCAE Grade 3	1	3	4
Any AE of >= CTCAE Grade 3 possibly related to treatment	0	0	0
Any SAE of >= CTCAE Grade 3	1	3	2
Any SAE of >= CTCAE Grade 3 possibly related to treatment	0	0	0

No statistical analysis provided for Number of Participants with Treatment-emergent Adverse Events (TEAEs)

2. Primary Outcome Measure: Number of Participants with Dose Limiting Toxicity (DLT) [ Time Frame: From Cycle 1 Day 1 to end of Cycle 1 (21 days) ]

Measure Type	Primary
Measure Name	Number of Participants with Dose Limiting Toxicity (DLT)
Measure Description	DLTs (in dose escalation Parts only) of AZD8853 in participants with selected advanced/metastatic solid tumors was assessed. The DLTs are specific adverse events defined as grade 3 (severe), grade 4 (life-threatening), and grade 5 (death) as per NCI-CTCAE version 5.0 non-hematological toxicity or hematological toxicity. This outcome measure was assessed only for substudy 1 Part A.
Time Frame	From Cycle 1 Day 1 to end of Cycle 1 (21 days)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
DLT evaluable set included enrolled participants who completed the DLT evaluation period (defined as 21 days after receiving the first infusion of IP) with at least 75% dosing and had completed safety evaluation requirements during the DLT evaluation period.

Reporting Groups

	Description
AZD8853 300 mg	Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 1000 mg	Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 3000 mg	Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.

Measured Values

	AZD8853 300 mg	AZD8853 1000 mg	AZD8853 3000 mg
Number of Participants Analyzed [units:participants]	3	6	6
Number of Participants with Dose Limiting Toxicity (DLT) [units: Participants]	0	0	0

No statistical analysis provided for Number of Participants with Dose Limiting Toxicity (DLT)

3. Secondary Outcome Measure: Objective Response Rate (ORR) [ Time Frame: First dose until progression of disease (PD) or last evaluable assessment in the absence of progression (1 Year) ]

Measure Type	Secondary
Measure Name	Objective Response Rate (ORR)
Measure Description	ORR was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR). This outcome measure was assessed only for substudy 1 Part A.
Time Frame	First dose until progression of disease (PD) or last evaluable assessment in the absence of progression (1 Year)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Response evaluable set included all dosed participants who had measurable disease at baseline. Here, "number of participants analyzed" specifies all participants who were evaluated for this outcome measure.

Reporting Groups

	Description
AZD8853 300 mg	Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 1000 mg	Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 3000 mg	Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.

Measured Values

	AZD8853 300 mg	AZD8853 1000 mg	AZD8853 3000 mg
Number of Participants Analyzed [units:participants]	3	6	7
Objective Response Rate (ORR) [units: Participants]	0	0	0

No statistical analysis provided for Objective Response Rate (ORR)

4. Secondary Outcome Measure: Disease Control Rate (DCR) at 15 Weeks [ Time Frame: 15 weeks ]

Measure Type	Secondary
Measure Name	Disease Control Rate (DCR) at 15 Weeks
Measure Description	Disease control was defined as a best overall response (BOR) of confirmed CR or PR or having stable disease (SD) (without subsequent cancer therapy) maintained for greater than or equal to (>=) 14 weeks (study week 15) from first IP. Disease control rate at study week 15 weeks (DCR-15) was defined as the percentage of participants who had disease control at study week 15 weeks. This outcome measure was assessed only for substudy 1 Part A.
Time Frame	15 weeks
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Response evaluable set included all dosed participants who had measurable disease at baseline.

Reporting Groups

	Description
AZD8853 300 mg	Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 1000 mg	Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 3000 mg	Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.

Measured Values

	AZD8853 300 mg	AZD8853 1000 mg	AZD8853 3000 mg
Number of Participants Analyzed [units:participants]	3	6	7
Disease Control Rate (DCR) at 15 Weeks [units: Participants]	1	0	1

No statistical analysis provided for Disease Control Rate (DCR) at 15 Weeks

5. Secondary Outcome Measure: Duration of Response (DOR) [ Time Frame: First documented response until date of first documented disease progression or study end (1 Year) ]

Measure Type	Secondary
Measure Name	Duration of Response (DOR)
Measure Description	The DOR was defined as the time from the date of first documented response (which was subsequently confirmed) until the date of documented progression or death in the absence of disease progression. This outcome measure was assessed only for substudy 1 Part A.
Time Frame	First documented response until date of first documented disease progression or study end (1 Year)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Response evaluable set included all dosed participants who had measurable disease at baseline. Only participants in the response evaluable set who had a response were planned to include. However, data was not evaluated for this outcome measure as there were no objective responses available for any participant at any dose level.

Reporting Groups

	Description
AZD8853 300 mg	Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 1000 mg	Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 3000 mg	Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.

Measured Values

	AZD8853 300 mg	AZD8853 1000 mg	AZD8853 3000 mg
Number of Participants Analyzed [units:participants]	0	0	0
Duration of Response (DOR) [units: Months] Median (Full Range)

No statistical analysis provided for Duration of Response (DOR)

6. Secondary Outcome Measure: Progression free survival (PFS) [ Time Frame: First dose until documented disease progression or study end (1 Year) ]

Measure Type	Secondary
Measure Name	Progression free survival (PFS)
Measure Description	The PFS was defined as the time from the start of study intervention until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the participant withdraws from study intervention or received another anti-cancer therapy prior to progression. This outcome measure was assessed only for substudy 1 Part A.
Time Frame	First dose until documented disease progression or study end (1 Year)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety set included all participants who received any amount of IP.

Reporting Groups

	Description
AZD8853 300 mg	Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 1000 mg	Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 3000 mg	Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.

Measured Values

	AZD8853 300 mg	AZD8853 1000 mg	AZD8853 3000 mg
Number of Participants Analyzed [units:participants]	3	6	7
Progression free survival (PFS) [units: Months] Median (Full Range)	1.31 (1.18 to 3.38)	1.23 (1.15 to 3.15)	1.25 (0.95 to 3.29)

No statistical analysis provided for Progression free survival (PFS)

7. Secondary Outcome Measure: Percentage Change from Baseline in Tumor Size [ Time Frame: Baseline (pre-treatment) up to Week 6 and Week 15 ]

Measure Type	Secondary
Measure Name	Percentage Change from Baseline in Tumor Size
Measure Description	Tumor size was the sum of the longest diameters (or short axis measurements for lymph nodes) of the target lesions (TLs). Percentage change in tumor size was determined for participants with measurable disease at baseline. Baseline for Response evaluation criteria in solid tumors (RECIST) version 1.1 was defined as the last evaluable assessment prior to first IP dose. This outcome measure was assessed only for substudy 1 Part A.
Time Frame	Baseline (pre-treatment) up to Week 6 and Week 15
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Response evaluable set included all dosed participants who had measurable disease at baseline. Here, "n" (number analyzed in each raw) signifies the participants with available data that were analyzed for each timepoint for this outcome measure.

Reporting Groups

	Description
AZD8853 300 mg	Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 1000 mg	Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 3000 mg	Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.

Measured Values

	AZD8853 300 mg	AZD8853 1000 mg	AZD8853 3000 mg
Number of Participants Analyzed [units:participants]	3	6	6
Percentage Change from Baseline in Tumor Size [units: Percentage change in tumor size] Median (Full Range)
Week 6	10.1 (-0.9 to 16.7)	10.9 (-0.9 to 41.4)	14.9 (1.5 to 37.4)
Week 15	46.5 (46.5 to 46.5)	5.7 (5.7 to 5.7)	70.0 (13.2 to 126.7)

No statistical analysis provided for Percentage Change from Baseline in Tumor Size

8. Secondary Outcome Measure: Overall Survival (OS) [ Time Frame: First dose until study end (1 Year) ]

Measure Type	Secondary
Measure Name	Overall Survival (OS)
Measure Description	Overall survival was defined as the time from the start of treatment until death due to any cause. This outcome measure was assessed only for substudy 1 Part A.
Time Frame	First dose until study end (1 Year)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety set included all participants who received any amount of IP.

Reporting Groups

	Description
AZD8853 300 mg	Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 1000 mg	Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 3000 mg	Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.

Measured Values

	AZD8853 300 mg	AZD8853 1000 mg	AZD8853 3000 mg
Number of Participants Analyzed [units:participants]	3	6	7
Overall Survival (OS) [units: Months] Median (90% Confidence Interval)	4.47 (2.92 to NA) ^[1]	5.45 (2.30 to NA) ^[1]	NA (0.95 to NA) ^[1]

No statistical analysis provided for Overall Survival (OS)

9. Secondary Outcome Measure: Percentage Change in Circulating Tumor Deoxyribonucleic Acid (ctDNA) Levels from Baseline [ Time Frame: Baseline (pre-treatment), Day 8 of Cycle 1, Days 1 and 8 of Cycle 2, Day 1 of Cycles 3, 4, 5, 7 (each cycle is equal to 21 days) ]

Measure Type	Secondary
Measure Name	Percentage Change in Circulating Tumor Deoxyribonucleic Acid (ctDNA) Levels from Baseline
Measure Description	Change in ctDNA is defined as the percentage change in ctDNA from baseline to each timepoint for the safety population. This outcome measure was assessed only for substudy 1 Part A.
Time Frame	Baseline (pre-treatment), Day 8 of Cycle 1, Days 1 and 8 of Cycle 2, Day 1 of Cycles 3, 4, 5, 7 (each cycle is equal to 21 days)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety set included all participants who received any amount of IP. Here, "number of participants analyzed" specifies all participants who were evaluated for this outcome measure and "n" (number analyzed in each raw) signifies the participants with available data that were analyzed for each timepoint for this outcome measure.

Reporting Groups

	Description
AZD8853 300 mg	Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 1000 mg	Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 3000 mg	Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.

Measured Values

	AZD8853 300 mg	AZD8853 1000 mg	AZD8853 3000 mg
Number of Participants Analyzed [units:participants]	3	6	6
Percentage Change in Circulating Tumor Deoxyribonucleic Acid (ctDNA) Levels from Baseline [units: Percentage change from baseline in ctDNA] Mean (Standard Deviation)
Cycle 1 Day 8	74.3700 (103.6200)	30.2546 (98.8909)	10.7795 (53.1457)
Cycle 2 Day 1	92.1105 (83.4783)	32.1430 (48.9060)	20.7386 (78.4507)
Cycle 2 Day 8	101.0003 (63.4941)	84.2143 (101.8080)	116.3071 (192.7165)
Cycle 3 Day 1	64.9807 (22.7578)	131.5277 (161.3495)	26.9231 (NA)^[1]
Cycle 4 Day 1	-8.3636 (NA)^[1]	50.2904 (54.8320)	21.4744 (NA)^[1]
Cycle 5 Day 1	64 (NA)^[1]	50.4363 (NA)^[1]
Cycle 7 Day 1	67.8182 (NA)^[1]

No statistical analysis provided for Percentage Change in Circulating Tumor Deoxyribonucleic Acid (ctDNA) Levels from Baseline

10. Secondary Outcome Measure: Maximum Observed Concentration (Cmax) of AZD8853 [ Time Frame: 0 hour, 15 minutes, 2 hours, 6 hours, 24 hours, 168 hours and 336 hours post EOI of Cycle 1 (each cycle equals to 21 days) ]

Measure Type	Secondary
Measure Name	Maximum Observed Concentration (Cmax) of AZD8853
Measure Description	The pharmacokinetic (PK) (Cmax) of AZD8853 in serum when administered in participants with selected advanced/metastatic solid tumors were assessed. This outcome measure was assessed only for substudy 1 Part A.
Time Frame	0 hour, 15 minutes, 2 hours, 6 hours, 24 hours, 168 hours and 336 hours post EOI of Cycle 1 (each cycle equals to 21 days)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK analysis set included all participants who received at least one dose of IP with at least one reportable concentration.

Reporting Groups

	Description
AZD8853 300 mg	Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 1000 mg	Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 3000 mg	Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.

Measured Values

	AZD8853 300 mg	AZD8853 1000 mg	AZD8853 3000 mg
Number of Participants Analyzed [units:participants]	3	6	7
Maximum Observed Concentration (Cmax) of AZD8853 [units: Micrograms per milliliter (ug/mL)] Mean (Standard Deviation)	76.70 (3.439)	339.5 (96.74)	1121 (225.9)

No statistical analysis provided for Maximum Observed Concentration (Cmax) of AZD8853

11. Secondary Outcome Measure: Area Under the Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUClast) of AZD8853 [ Time Frame: 0 hour, 15 minutes, 2 hours, 6 hours, 24 hours, 168 hours and 336 hours post EOI of Cycle 1 (each cycle equals to 21 days) ]

Measure Type	Secondary
Measure Name	Area Under the Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUClast) of AZD8853
Measure Description	The PK (AUClast) of AZD8853 in serum when administered in participants with selected advanced/metastatic solid tumors were assessed. This outcome measure was assessed only for substudy 1 Part A.
Time Frame	0 hour, 15 minutes, 2 hours, 6 hours, 24 hours, 168 hours and 336 hours post EOI of Cycle 1 (each cycle equals to 21 days)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK analysis set included all participants who received at least one dose of IP with at least one reportable concentration.

Reporting Groups

	Description
AZD8853 300 mg	Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 1000 mg	Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 3000 mg	Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.

Measured Values

	AZD8853 300 mg	AZD8853 1000 mg	AZD8853 3000 mg
Number of Participants Analyzed [units:participants]	3	6	7
Area Under the Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUClast) of AZD8853 [units: Hoursmicrogram per milliliter (hug/mL)] Mean (Standard Deviation)	10080 (1789)	49210 (12130)	161100 (43070)

No statistical analysis provided for Area Under the Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUClast) of AZD8853

12. Secondary Outcome Measure: Partial Area Under the Plasma Concentration-time Curve from Time 0 to 504 hours post dose (AUC[0-504 hours]) of AZD8853 [ Time Frame: 0 hour, 15 minutes, 2 hours, 6 hours, 24 hours, 168 hours and 336 hours post EOI of Cycle 1 (each cycle equals to 21 days) ]

Measure Type	Secondary
Measure Name	Partial Area Under the Plasma Concentration-time Curve from Time 0 to 504 hours post dose (AUC[0-504 hours]) of AZD8853
Measure Description	The PK (AUC[t1-t2]) of AZD8853 in serum when administered in participants with selected advanced/metastatic solid tumors were assessed. This outcome measure was assessed only for substudy 1 Part A.
Time Frame	0 hour, 15 minutes, 2 hours, 6 hours, 24 hours, 168 hours and 336 hours post EOI of Cycle 1 (each cycle equals to 21 days)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK analysis set included all participants who received at least one dose of IP with at least one reportable concentration.

Reporting Groups

	Description
AZD8853 300 mg	Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 1000 mg	Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 3000 mg	Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.

Measured Values

	AZD8853 300 mg	AZD8853 1000 mg	AZD8853 3000 mg
Number of Participants Analyzed [units:participants]	3	6	7
Partial Area Under the Plasma Concentration-time Curve from Time 0 to 504 hours post dose (AUC[0-504 hours]) of AZD8853 [units: h*ug/mL] Mean (Standard Deviation)	11870 (2385)	57230 (14760)	189400 (56040)

No statistical analysis provided for Partial Area Under the Plasma Concentration-time Curve from Time 0 to 504 hours post dose (AUC[0-504 hours]) of AZD8853

13. Secondary Outcome Measure: Area Under the Plasma Concentration-time Curve from Zero to Infinity (AUCinf) of AZD8853 [ Time Frame: 0 hour, 15 minutes, 2 hours, 6 hours, 24 hours, 168 hours and 336 hours post EOI of Cycle 1 (each cycle equals to 21 days) ]

Measure Type	Secondary
Measure Name	Area Under the Plasma Concentration-time Curve from Zero to Infinity (AUCinf) of AZD8853
Measure Description	The PK (AUCinf) of AZD8853 in serum when administered in participants with selected advanced/metastatic solid tumors were assessed. This outcome measure was assessed only for substudy 1 Part A.
Time Frame	0 hour, 15 minutes, 2 hours, 6 hours, 24 hours, 168 hours and 336 hours post EOI of Cycle 1 (each cycle equals to 21 days)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK analysis set included all participants who received at least one dose of IP with at least one reportable concentration.

Reporting Groups

	Description
AZD8853 300 mg	Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 1000 mg	Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 3000 mg	Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.

Measured Values

	AZD8853 300 mg	AZD8853 1000 mg	AZD8853 3000 mg
Number of Participants Analyzed [units:participants]	3	6	7
Area Under the Plasma Concentration-time Curve from Zero to Infinity (AUCinf) of AZD8853 [units: h*ug/mL] Mean (Standard Deviation)	14580 (4136)	67480 (18490)	223700 (79270)

No statistical analysis provided for Area Under the Plasma Concentration-time Curve from Zero to Infinity (AUCinf) of AZD8853

14. Secondary Outcome Measure: Number of Participants with Positive Anti-drug Antibody (ADA) of AZD8853 [ Time Frame: From Day 1 up to 90 (±7 days) days after the last dose of AZD8853 (1 year) ]

Measure Type	Secondary
Measure Name	Number of Participants with Positive Anti-drug Antibody (ADA) of AZD8853
Measure Description	The immunogenicity of AZD8853 in participants with selected advanced/metastatic solid tumors were assessed. This outcome measure was assessed only for substudy 1 Part A.
Time Frame	From Day 1 up to 90 (±7 days) days after the last dose of AZD8853 (1 year)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Immunogenicity analysis set included all participants who received at least one dose of IP who have a non-missing baseline ADA result and at least 1 non-missing post-baseline ADA result.

Reporting Groups

	Description
AZD8853 300 mg	Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 1000 mg	Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 3000 mg	Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.

Measured Values

	AZD8853 300 mg	AZD8853 1000 mg	AZD8853 3000 mg
Number of Participants Analyzed [units:participants]	3	6	6
Number of Participants with Positive Anti-drug Antibody (ADA) of AZD8853 [units: Participants]	1	1	0

No statistical analysis provided for Number of Participants with Positive Anti-drug Antibody (ADA) of AZD8853

15. Secondary Outcome Measure: Percentage Change from Baseline in Circulating Growth Differentiation Factor 15 (GDF15) Serum Levels [ Time Frame: 0 hours post EOI of Cycle 1 Day 1, Day 1 (Pre-dose) of Cycles 2 and 3 (each cycle equals to 21 days) and 90-days post EOT of 90 days follow-up ]

Measure Type	Secondary
Measure Name	Percentage Change from Baseline in Circulating Growth Differentiation Factor 15 (GDF15) Serum Levels
Measure Description	The pharmacodynamics (PD) activity of AZD8853 by assessment of candidate biomarkers in participants with selected advanced/metastatic solid tumors were assessed. This outcome measure was assessed only for substudy1 Part A. End of infusion= EOI; End of treatment= EOT
Time Frame	0 hours post EOI of Cycle 1 Day 1, Day 1 (Pre-dose) of Cycles 2 and 3 (each cycle equals to 21 days) and 90-days post EOT of 90 days follow-up
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PD analysis set included all participants who received at least one dose of IP with at least one reportable concentration. Here, "number of participants analyzed" specifies all participants who were evaluated for this outcome measure and "n" (number analyzed in each raw) signifies the participants with available data that were analyzed for each timepoint for this outcome measure.

Reporting Groups

	Description
AZD8853 300 mg	Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 1000 mg	Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 3000 mg	Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.

Measured Values

	AZD8853 300 mg	AZD8853 1000 mg	AZD8853 3000 mg
Number of Participants Analyzed [units:participants]	3	6	6
Percentage Change from Baseline in Circulating Growth Differentiation Factor 15 (GDF15) Serum Levels [units: Percentage change from baseline in GDF15] Mean (Standard Deviation)
Cycle 1 Day 1: 0 hours post EOI	-97.7850 (0.1917)	-99.2637 (0.1161)	-99.7472 (NA)^[1]
Cycle 2 Day 1 (Pre-dose)	324.2284 (103.7778)	411.2175 (345.6173)	165.9668 (82.9703)
Cycle 3 Day 1 (Pre-dose)	636.8307 (NA)^[1]	770.4598 (520.3336)	212.5270 (111.5861)
90 Days Follow-Up: 90 days post EOT	2164.2547 (NA)^[1]	1311.2845 (NA)^[1]	2513.913 (NA)^[1]

No statistical analysis provided for Percentage Change from Baseline in Circulating Growth Differentiation Factor 15 (GDF15) Serum Levels

Serious Adverse Events

Time Frame	From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year).
Additional Description	Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.

Reporting Groups

	Description
AZD8853 300 mg	Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 1000 mg	Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 3000 mg	Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.

Serious Adverse Events

AZD8853 300 mg

AZD8853 1000 mg

AZD8853 3000 mg

Total, serious adverse events

# participants affected / at risk

2/3 (66.67%)

3/6 (50.00%)

2/7 (28.57%)

Vascular disorders

Syncope¹

# participants affected / at risk

1/3 (33.33%)

0/6 (0.00%)

0/7 (0.00%)

Infections and infestations

COVID-19¹

# participants affected / at risk

1/3 (33.33%)

0/6 (0.00%)

0/7 (0.00%)

Infections and infestations

Clostridium difficile infection¹

# participants affected / at risk

1/3 (33.33%)

0/6 (0.00%)

0/7 (0.00%)

Gastrointestinal disorders

Anal fistula¹

# participants affected / at risk

1/3 (33.33%)

0/6 (0.00%)

0/7 (0.00%)

Infections and infestations

Sepsis¹

# participants affected / at risk

1/3 (33.33%)

0/6 (0.00%)

0/7 (0.00%)

Investigations

Blood bilirubin increased¹

# participants affected / at risk

0/3 (0.00%)

1/6 (16.67%)

0/7 (0.00%)

Vascular disorders

Embolism¹

# participants affected / at risk

0/3 (0.00%)

1/6 (16.67%)

0/7 (0.00%)

Cardiac disorders

Cardiac arrest¹

# participants affected / at risk

0/3 (0.00%)

1/6 (16.67%)

0/7 (0.00%)

Musculoskeletal and connective tissue disorders

Back pain¹

# participants affected / at risk

0/3 (0.00%)

1/6 (16.67%)

0/7 (0.00%)

Gastrointestinal disorders

Small intestinal obstruction¹

# participants affected / at risk

0/3 (0.00%)

0/6 (0.00%)

1/7 (14.29%)

Injury, poisoning and procedural complications

Femoral neck fracture¹

# participants affected / at risk

0/3 (0.00%)

0/6 (0.00%)

1/7 (14.29%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 26.0

Other Adverse Events

Time Frame	From screening (Day -28 to Day -1) up to 90 (±7 days) days after the last dose of AZD8853 (1 Year).
Additional Description	Safety set included all participants who received any amount of IP. All the adverse events from Screening till study termination have been presented here before and after receiving treatment.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
AZD8853 300 mg	Participants with advanced/metastatic solid tumors received AZD8853 300 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 1000 mg	Participants with advanced/metastatic solid tumors received AZD8853 1000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.
AZD8853 3000 mg	Participants with advanced/metastatic solid tumors received AZD8853 3000 mg every 3 weeks until progressive disease, unacceptable toxicity, or withdrawal of consent.

Other Adverse Events

AZD8853 300 mg

AZD8853 1000 mg

AZD8853 3000 mg

Total, other (not including serious) adverse events

# participants affected / at risk

3/3 (100.00%)

4/6 (66.67%)

6/7 (85.71%)

Musculoskeletal and connective tissue disorders

Muscular weakness¹

# participants affected / at risk

1/3 (33.33%)

0/6 (0.00%)

0/7 (0.00%)

General disorders

Pyrexia¹

# participants affected / at risk

2/3 (66.67%)

0/6 (0.00%)

1/7 (14.29%)

Metabolism and nutrition disorders

Decreased appetite¹

# participants affected / at risk

2/3 (66.67%)

0/6 (0.00%)

2/7 (28.57%)

Investigations

Blood alkaline phosphatase increased¹

# participants affected / at risk

1/3 (33.33%)

0/6 (0.00%)

0/7 (0.00%)

Blood and lymphatic system disorders

Anaemia¹

# participants affected / at risk

1/3 (33.33%)

0/6 (0.00%)

0/7 (0.00%)

Metabolism and nutrition disorders

Dehydration¹

# participants affected / at risk

1/3 (33.33%)

0/6 (0.00%)

0/7 (0.00%)

Gastrointestinal disorders

Diarrhoea¹

# participants affected / at risk

1/3 (33.33%)

1/6 (16.67%)

3/7 (42.86%)

Vascular disorders

Hypotension¹

# participants affected / at risk

1/3 (33.33%)

0/6 (0.00%)

0/7 (0.00%)

Metabolism and nutrition disorders

Hyponatraemia¹

# participants affected / at risk

1/3 (33.33%)

0/6 (0.00%)

0/7 (0.00%)

Gastrointestinal disorders

Abdominal pain¹

# participants affected / at risk

1/3 (33.33%)

1/6 (16.67%)

3/7 (42.86%)

General disorders

Chills¹

# participants affected / at risk

1/3 (33.33%)

0/6 (0.00%)

1/7 (14.29%)

Musculoskeletal and connective tissue disorders

Sacral pain¹

# participants affected / at risk

1/3 (33.33%)

0/6 (0.00%)

0/7 (0.00%)

Cardiac disorders

Sinus tachycardia¹

# participants affected / at risk

1/3 (33.33%)

0/6 (0.00%)

0/7 (0.00%)

Gastrointestinal disorders

Constipation¹

# participants affected / at risk

1/3 (33.33%)

1/6 (16.67%)

1/7 (14.29%)

Metabolism and nutrition disorders

Hypokalaemia¹

# participants affected / at risk

1/3 (33.33%)

0/6 (0.00%)

0/7 (0.00%)

Respiratory, thoracic and mediastinal disorders

Cough¹

# participants affected / at risk

1/3 (33.33%)

1/6 (16.67%)

1/7 (14.29%)

General disorders

Fatigue¹

# participants affected / at risk

0/3 (0.00%)

1/6 (16.67%)

2/7 (28.57%)

Vascular disorders

Haematoma¹

# participants affected / at risk

0/3 (0.00%)

1/6 (16.67%)

0/7 (0.00%)

Musculoskeletal and connective tissue disorders

Back pain¹

# participants affected / at risk

0/3 (0.00%)

2/6 (33.33%)

0/7 (0.00%)

Musculoskeletal and connective tissue disorders

Myalgia¹

# participants affected / at risk

0/3 (0.00%)

0/6 (0.00%)

1/7 (14.29%)

Musculoskeletal and connective tissue disorders

Arthralgia¹

# participants affected / at risk

0/3 (0.00%)

0/6 (0.00%)

1/7 (14.29%)

General disorders

Localised oedema¹

# participants affected / at risk

0/3 (0.00%)

0/6 (0.00%)

1/7 (14.29%)

Cardiac disorders

Supraventricular tachycardia¹

# participants affected / at risk

0/3 (0.00%)

1/6 (16.67%)

0/7 (0.00%)

Gastrointestinal disorders

Abdominal pain lower¹

# participants affected / at risk

0/3 (0.00%)

1/6 (16.67%)

0/7 (0.00%)

Gastrointestinal disorders

Nausea¹

# participants affected / at risk

0/3 (0.00%)

2/6 (33.33%)

0/7 (0.00%)

Gastrointestinal disorders

Vomiting¹

# participants affected / at risk

0/3 (0.00%)

1/6 (16.67%)

0/7 (0.00%)

Gastrointestinal disorders

Gastrooesophageal reflux disease¹

# participants affected / at risk

0/3 (0.00%)

0/6 (0.00%)

1/7 (14.29%)

Gastrointestinal disorders

Oral pain¹

# participants affected / at risk

0/3 (0.00%)

0/6 (0.00%)

1/7 (14.29%)

Gastrointestinal disorders

Abdominal distension¹

# participants affected / at risk

0/3 (0.00%)

0/6 (0.00%)

1/7 (14.29%)

Immune system disorders

Hypersensitivity¹

# participants affected / at risk

0/3 (0.00%)

0/6 (0.00%)

1/7 (14.29%)

Infections and infestations

COVID-19 pneumonia¹

# participants affected / at risk

0/3 (0.00%)

0/6 (0.00%)

1/7 (14.29%)

Infections and infestations

Tooth infection¹

# participants affected / at risk

0/3 (0.00%)

0/6 (0.00%)

1/7 (14.29%)

Injury, poisoning and procedural complications

Vascular access complication¹

# participants affected / at risk

0/3 (0.00%)

1/6 (16.67%)

0/7 (0.00%)

Injury, poisoning and procedural complications

Fall¹

# participants affected / at risk

0/3 (0.00%)

0/6 (0.00%)

1/7 (14.29%)

Investigations

Weight decreased¹

# participants affected / at risk

0/3 (0.00%)

0/6 (0.00%)

1/7 (14.29%)

Investigations

Aspartate aminotransferase increased¹

# participants affected / at risk

0/3 (0.00%)

0/6 (0.00%)

1/7 (14.29%)

Investigations

Alanine aminotransferase increased¹

# participants affected / at risk

0/3 (0.00%)

0/6 (0.00%)

1/7 (14.29%)

Investigations

Blood creatine phosphokinase increased¹

# participants affected / at risk

0/3 (0.00%)

0/6 (0.00%)

1/7 (14.29%)

Investigations

Weight increased¹

# participants affected / at risk

0/3 (0.00%)

0/6 (0.00%)

1/7 (14.29%)

Metabolism and nutrition disorders

Hypophosphataemia¹

# participants affected / at risk

0/3 (0.00%)

1/6 (16.67%)

0/7 (0.00%)

Metabolism and nutrition disorders

Hypomagnesaemia¹

# participants affected / at risk

0/3 (0.00%)

1/6 (16.67%)

0/7 (0.00%)

Nervous system disorders

Peripheral sensory neuropathy¹

# participants affected / at risk

0/3 (0.00%)

0/6 (0.00%)

1/7 (14.29%)

Nervous system disorders

Hemiparesis¹

# participants affected / at risk

0/3 (0.00%)

0/6 (0.00%)

1/7 (14.29%)

Psychiatric disorders

Insomnia¹

# participants affected / at risk

0/3 (0.00%)

1/6 (16.67%)

1/7 (14.29%)

Renal and urinary disorders

Urine odour abnormal¹

# participants affected / at risk

0/3 (0.00%)

0/6 (0.00%)

1/7 (14.29%)

Renal and urinary disorders

Urinary incontinence¹

# participants affected / at risk

0/3 (0.00%)

0/6 (0.00%)

1/7 (14.29%)

Respiratory, thoracic and mediastinal disorders

Pulmonary embolism¹

# participants affected / at risk

0/3 (0.00%)

0/6 (0.00%)

1/7 (14.29%)

Respiratory, thoracic and mediastinal disorders

Productive cough¹

# participants affected / at risk

0/3 (0.00%)

0/6 (0.00%)

1/7 (14.29%)

Vascular disorders

Hypertension¹

# participants affected / at risk

0/3 (0.00%)

1/6 (16.67%)

0/7 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 26.0

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: No unpublished information contained herein may be disclosed without prior written approval from AstraZeneca. Access to this document must be restricted to relevant parties. This document contains trade secrets and confidential commercial information, disclosure of which is prohibited without providing advance notice to AstraZeneca and opportunity to object.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
This study was terminated early as per protocol Section 4.4, based on overall risk-benefit profile observed to date. No safety concerns reported. Only Sub-study 1 Part A was started; Parts B & C were not started.

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

CSR Synopsis
Download
SAP redacted
Download
CSP redacted
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

CSR Synopsis

SAP redacted

CSP redacted

Trial Results Summaries